DESCRIPTION (provide by applicant) Toxic metals are a major concern both at Superfund and other waste sites and in the environment in general. Eight of the top fifty substances on the Agency for Toxic Substances and Disease Registry (ATSDR) priority list are toxic metals, including the top three priority substances, arsenic, lead and mercury. Eight of the twenty-two substances on the U.S. Environmental Protection Agency (EPA) Office of Solid Waste and Emergency Response (OSWER) list of chemicals of highest concern at Superfund sites are toxic metals. Over 60% of the 1,200 current Superfund sites contain substantial contamination by toxic metals, and arsenic alone is present in over 70% of these sites. The overall objective of this renewal of the Dartmouth SBRP Project (Toxic Metals in the Northeast: From Biological to Environmental Implications) is to understand how arsenic and other toxic metals contribute to adverse effects on human health and the environment. The investigators have a particular emphasis on arsenic, which is the focus of research in all six of the research projects and which serves as a major integrator of the Program across disciplinary boundaries; they also have an emphasis on mercury, cadmium and lead. Other major integrating themes of the Program are the extensive application of toxicogenomics and biomarkers, and the analysis of multiple stressors as a major mechanism underlying the environmental health impact of toxic metals. This Program consists of four biomedical (Projects 2, 4, 5, 8) and two nonbiomedical Research Projects (Projects 6 and 7); three Scientific Support Cores (A, B, D); a Training Core and Community Outreach Core; and Administrative and Translation Cores. Research projects include Project 2 (Arsenic as an endocrine disruptor), Project 4 (Arsenic epidemiology, biomarkers and exposure assessment), Project 5 (Toxic metal interactions with cellular proteins), Project 6 (Arsenic hydrogeochemistry at the Coakley Superfund site), Project 7 (Trophic transfer of toxic metals in aquatic food webs) and Project 8 (Arsenic and ABC transporters). Scientific Support Cores include a Molecular Biology & Proteomics Core (MBP) (Core A), a Trace Elements Analysis Core (Core B) and a Biomarkers Core (Core D). The Community Outreach Project is focused on lead poisoning prevention awareness, targeting underserved minority populations in Manchester NH, and involves collaborations with agencies of the State of New Hampshire and the City of Manchester and several local non-profit community groups. The multi-disciplinary nature of this Program, combined with its unique Program-wide focus on arsenic and other toxic metals and its other integrating themes is designed to create and foster a truly interdisciplinary yet focused research, education, outreach and training program.